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Int J Biol Sci 2024; 20(5):1833-1854. doi:10.7150/ijbs.91492 This issue Cite

Review

Histone lactylation: from tumor lactate metabolism to epigenetic regulation

Xiaoning Yu^1,2,3,4,#, Jing Yang^1,2,3,4,#, Jin Xu^1,2,3,4,#, Haoqi Pan^1,2,3,4, Wei Wang^1,2,3,4, Xianjun Yu^5,6,7,8✉, Si Shi^{9,10,11,12✉}

1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
3. Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China.
4. Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China.
5. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No.270 Dong' An Road, Shanghai, People's Republic of China.
6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
7. Shanghai Pancreatic Cancer Institute, No.270 Dong' An Road, 200032, Shanghai, People's Republic of China.
8. Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China.
9. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No.270 Dong' An Road, Shanghai, People's Republic of China.
10. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
11. Shanghai Pancreatic Cancer Institute, No.270 Dong' An Road, 200032, Shanghai, People's Republic of China.
12. Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China.
#These authors contributed equally to this work.

✉ Corresponding authors: yuxianjunorg; shisiorg.

Abstract

The Warburg Effect is one of the most well-known cancer hallmarks. This metabolic pattern centered on lactate has extremely complex effects on various aspects of tumor microenvironment, including metabolic remodeling, immune suppression, cancer cell migration, and drug resistance development. Based on accumulating evidence, metabolites are likely to participate in the regulation of biological processes in the microenvironment and to form a feedback loop. Therefore, further revealing the key mechanism of lactate-mediated oncological effects is a reasonable scientific idea. The discovery and refinement of histone lactylation in recent years has laid a firm foundation for the above idea. Histone lactylation is a post-translational modification that occurs at lysine sites on histones. Specific enzymes, known as “writers” and “erasers”, catalyze the addition or removal, respectively, of lactacyl group at target lysine sites. An increasing number of investigations have reported this modification as key to multiple cellular procedures. In this review, we discuss the close connection between histone lactylation and a series of biological processes in the tumor microenvironment, including tumorigenesis, immune infiltration, and energy metabolism. Finally, this review provides insightful perspectives, identifying promising avenues for further exploration and potential clinical application in this field of research.

Keywords: Warburg Effect, Lactate, Histone lactylation, Tumor microenvironment

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